Reports from England have confirmed that centre Manu Tuilagi will miss Saturday's Calcutta Cup clash with Scotland while London Irish's Alex Corbisiero will sit out the entire Six Nations campaign.

Tuilagi has been struggling with an ankle injury he suffered earlier in January and missed Leicester's key Heineken Cup clash with Toulouse on January 20. England had previously given the centre a deadline of Tuesday to prove his fitness ahead of Saturday's match, but the management will now give him a chance to fully recover ahead of England's second Test of the tournament against Ireland on February 10.

The news will come as a massive blow to Stuart Lancaster and England. Tuilagi is England's most potent attacking weapon and he led the destruction of New Zealand last month, scoring one try and playing a key role in the creation of two others.

"By the end of the week we expect Manu to be running fully and changing direction," Lancaster said. "The message I'm receiving from the medical team is that he will be training fully by Tuesday or Wednesday next week, but I'll need to make a call earlier in the week. He won't be training properly until at least Friday.

"Manu is a big loss - he was outstanding against New Zealand. But he missed the first two games of last year's Six Nations because of a hamstring and it's an opportunity for someone else. It's disappointing for him, but it's not a long-term injury so he'll be back soon."

With Tuilagi out, England will now have to look to a new centre partnership for Saturday's game. Lancaster has previously alluded to Gloucester's Billy Twelvetrees or London Irish's Jonathan Joseph getting the nod. "There are different options - you could put Brad (Barritt) at 12 and JJ at 13 or put Billy at 12 and Brad at 13," Lancaster explained.

When England trained at Headingley on Friday, Lancaster did not give away any indication of which way he will turn with both Twelvetrees and Joseph running off Barritt. Another option could be to switch either Owen Farrell or Toby Flood to inside centre with the other starting at fly-half.

"We have a pretty good idea of how we'll rejig the midfield. We have our thoughts," Lancaster added. "It changes the emphasis a little bit, but it won't fundamentally affect the way we play. Brad will be in the equation and we need to make sure we can still break the gainline and have physical defenders. We've got to have the ability to get across the gainline and defend."

And England have also confirmed that loose-head Corbisiero will miss the tournament. He has been trying to battle back to full fitness from a knee injury and underwent surgery earlier this week to remove a "loose body". The initial outlook on Corbisiero's knee problem was that he could return against France on February 23, but London Irish director of rugby Brian Smith revealed last night that his rehabilitation will take longer. Lancaster, however, denies Smith's suggestion that the injury is more grave than has been made public.

"The reality is the surgeons recommended two weeks rest and said it would then take six to eight weeks to be back playing, so that will rule him out of the Six Nations," said Lancaster. "Hopefully he'll be back around the final game against Wales, but the reality is he'll have to play two or three Premiership games first.

"It's a shame because everything I heard about the operation was positive, but it's going to take a while to get right. Everyone's positive and upbeat about his recovery. Alex is a big loss, but Joe Marler has played well for Harlequins recently. Mako Vunipola is improving all the time and Nick Wood was outstanding for the Saxons."

Gloucester fly-half Freddie Burns has been ruled out against Scotland and Ireland with knee ligament injury damage, while Wasps number eight Billy Vunipola is struggling with an ankle problem.